The overall goal of this project is to develop an understanding of the genetic as well as environmental influences that are involved in the etiology of human esophageal cancer. These studies are being conducted in North Central China where rates of esophageal cancer are highest in the world, and where extraordinary familial aggregation of the disease exists. A series of studies to evaluate the role of genetics in the etiology of esophageal cancer have been conducted, including studies of family history of esophageal cancer, familial aggregation, and segregation analyses of family pedigrees from high risk families. Future studies will search for esophageal cancer susceptibility genes through genomic searches of tumor/nontumor tissue and prospective followup of high risk families for linkage analysis. This study is being conducted collaboratively with scientists at the Chinese Academy of Medical Sciences, the National Center for Human Genome Research, and the Fox Chase Cancer Center.